Diltiazem Hydrochloride

Cardiovascular Drug

Drug class: Calcium-channel Blocker, CCB

Diltiazem (HERBESSER)（中文：地爾硫卓） is a benzothiazepine calcium-channel blocker. It is used for:

a. Prevention and long-term treatment of angina.

b. Treatment of mild to moderate hypertension.

Pronunciation

Diltiazem hydrochloride controlled-released 100mg

Diltiazem hydrochloride controlled-released 30mg

Diltiazem hydrochloride controlled-released 60mg

Generic Name:	Diltiazem
Brand Name:	HERBESSER
Class:	Cardiovascular Drug
Subclass:	Calcium-channel Blocker, CCB
Legal Classification:	P1S1S3

Drug Names

Generic Name 藥物化學名稱	HA Code 藥物代碼	Legal Classification法律藥物分類	Brand Name 品牌名稱
Diltiazem HCL CR Tablet 30mg	DILT01	P1S1S3	HERBESSER
Diltiazem HCL CR Tablet 60mg	DILT02	P1S1S3	HERBESSER
Diltiazem HCL SR Capsule 100mg	DILT07	P1S1S3	HERBESSER
Diltiazem HCL SR Capsule 200mg	DILT08	P1S1S3	HERBESSER

Mechanism of Action

Diltiazem is a peripheral and coronary vasodilator. It also inhibits cardiac conduction, particularly at the sino-atrial and atrioventricular nodes. Diltiazem works by lowering your blood pressure and makes it easier for your heart to pump blood around your body.

In angina, diltiazem works by improving the blood and oxygen supply to your heart. Angina is chest pain that comes on when not enough blood gets to the muscles of the heart. This usually happens because the arteries going to the heart become hardened and narrowed.

Route of Administration

Diltiazem is given orally in a sustained-release formulation.

Dosage

Your dose of diltiazem depends on why you need the medicine and what kind your doctor has prescribed. It is important to keep taking the same brand of diltiazem once you have started.

Agina

• BY MOUTH
• Adult: Initially 60 mg 3 times a day, adjusted according to response; maximum 360 mg per day.
• Elderly: initially 60 mg twice daily, adjusted according to response; maximum 360 mg per day (the heart rate should be monitored regularly and should not fall below 50 beats/minute).

Hypertension

• BY MOUTH
• Adult: an initial dose is 90 to 120 mg twice daily, increased as required to a maximum of 360 mg daily.

Side Effects

The following definitions of frequencies are used:

Very common ≥ 1/10

Common ≥ 1/100 to < 1/10

Uncommon ≥ 1/1,000 to < 1/100

Rare ≥ 1/10,000 to < 1/1,000

Very rare < 1/10,000

System Organ Class	Frequency	Adverse reactions
Nervous system disorder	Common	Headache, dizziness
Cardiac disorders	Common	Atrioventricular block, bradycardia
Vascular disorders	Common	Flushing, orthostatic hypotension
Gastro-intestinal disorders	Common	Gastric pain, dyspepsia,nausea, constipation
General disorders	Common	Peripheral oedema, notably of ankles
Skin	Common	Erythema

Pharmacokinetics

Absorption

Diltiazem is almost completely absorbed from the gastrointestinal tract after oral doses, but undergoes extensive first-pass hepatic metabolism resulting in a bioavailability of about 40%.

Peak plasma concentrations occur about 3 to 8 hours after an oral dose, depending on the dosage form

Distribution

Diltiazem is about 80% bound to plasma proteins. It is distributed into breast milk.

Metabolism

It is extensively metabolized in the liver, mainly by the cytochrome P450 isoenzyme CYP3A4.

Elimination

The half-life of diltiazem is reported to be about 3 to 8 hours, again depending on the dosage form. About 2 to 4% of a dose is excreted in urine as unchanged diltiazem with the remainder excreted as metabolites in bile and urine.

Drug Management

Drug Interaction:

Diltiazem is metabolized in the liver by cytochrome P450 3A4 (CYP3A4). Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral administration) or the clearance of diltiazem.

The extent as well as the duration of interactions should be taken into account when administering diltiazem together with the following drugs:

Rifampicin: Rifampicin strongly induces the cytochrome P450 3A4 system. Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin. The patient should be carefully monitored when initiating or discontinuing rifampicin treatment.

Interactions leading to increased plasma concentration of diltiazem

CYP3A4 enzyme inhibitors have been shown to cause an increase in diltiazem plasma concentrations. In case of clinically significant adverse events due to elevated diltiazem exposure when combined with strong CYP3A4 inhibitors, adjustment of diltiazem dose and/or discontinuation of the CYP3A4 inhibitor should be considered.

Examples:

- Cimetidine

- Erythromycin

- Itraconazole

- Ketoconazole

- Certain flavonoids present in grapefruit juice

Diltiazem tablets should not be taken together with grapefruit juice.

Interactions leading to decreased plasma concentration of diltiazem

Enzyme inducers of the cytochrome P450 3A4 system have been shown to cause a decrease in plasma concentrations of diltiazem.

In case of lack of efficacy due to decreased diltiazem when combined with potent inducers of CYP3A4, adjustment of diltiazem dose and/or discontinuation of the CYP3A4 inducer should be considered.

Examples:

- Phenytoin

- Carbamazepine

- Rifampicin

- Barbiturates

- Hypericum perforatum (Saint John's wort)

Additional interactions

The simultaneous administration of diltiazem and digoxin/amiodarone may lead to increased risk of bradycardia; caution is required particularly in elderly and when high doses are used.

Diltiazem is an inhibitor of CYP3A4 and has been shown to significantly increase some statins (e.g. atorvastatin and simvastatin). The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with statins as mentioned.

Contraindication:

• Acute porphyrias
• Left ventricular failure with pulmonary congestion
• Second- or third-degree atrioventricular block
• Severe bradycardia
• Sick sinus syndrome

Pregnancy: avoid

Breast Feeding: significant amount present in milk – no evidence of harm but avoid unless no safer alternative.

Hepatic Impairment: reduce dose

Renal Impairment: start with smaller dose

FAQ

How should I take the tablet?

Swallow the tablet whole with a drink of water. Do not crush the tablet.

What should I avoid while taking?

Avoid eating grapefruit or drinking grapefruit juice while taking diltiazem. Grapefruit juice can increase diltiazem in your body and make side effects worse, such as flushing or getting headaches.

What happen if I miss a dose?

If you forget to take a dose and you usually take diltiazem:

• Once a day – take it as soon as you remember, unless it is less than 12 hours until your next dose. In this case, leave out the missed dose and take your next dose at the usual time.
• Twice a day – take it as soon as you remember, unless it is less than 4 hours until your next dose. In this case, leave out the missed dose and take you next dose at the usual time.
• Three times a day – leave out that dose and take your next dose at the usual time.

Do not take a double dose to make up for a forgotten one.